17-28364299-A-G

Position:

• chr17-28364299-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080837.4(SEBOX):​c.542T>C​(p.Leu181Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,604,922 control chromosomes in the GnomAD database, including 495,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.83 (52846 hom., cov: 32)
  • Exomes 𝑓: 0.78 (443053 hom.)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

SEBOX (HGNC:32942): (SEBOX homeobox) Homeodomain proteins, such as SEBOX, play a key role in coordinating gene expression during development (Cinquanta et al., 2000 [PubMed 10922053]).[supplied by OMIM, Mar 2008]

ENSG00000273171 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.989246E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEBOX	NM_001080837.4	c.542T>C	p.Leu181Ser	missense_variant	3/3	ENST00000536498.6	NP_001074306.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEBOX	ENST00000536498.6	c.542T>C	p.Leu181Ser	missense_variant	3/3	5	NM_001080837.4	ENSP00000444503.3
ENSG00000273171	ENST00000555059.2	c.*393T>C		3_prime_UTR_variant	4/4	4		ENSP00000452347.3
ENSG00000258924	ENST00000591482.1	n.555+3452A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125768 AN: 152076 Hom.: 52793 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.846

GnomAD3 exomes AF: 0.795 AC: 187261 AN: 235462 Hom.: 75225 AF XY: 0.794 AC XY: 101160 AN XY: 127446

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.996

Gnomad SAS exome AF: 0.828

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.779 AC: 1131350 AN: 1452728 Hom.: 443053 Cov.: 47 AF XY: 0.779 AC XY: 562497 AN XY: 721670

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.773

Gnomad4 ASJ exome AF: 0.790

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.830

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.827 AC: 125881 AN: 152194 Hom.: 52846 Cov.: 32 AF XY: 0.823 AC XY: 61230 AN XY: 74404

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.848

Alfa AF: 0.780 Hom.: 95368

Bravo AF: 0.844

TwinsUK AF: 0.764 AC: 2832

ALSPAC AF: 0.765 AC: 2949

ESP6500AA AF: 0.959 AC: 4023

ESP6500EA AF: 0.777 AC: 6566

ExAC AF: 0.795 AC: 96122

Asia WGS AF: 0.905 AC: 3145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.88
DANN	Benign	0.72
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.34	T
REVEL	Benign	0.23
Sift4G	Benign	0.77	T
Vest4		0.071
ClinPred		0.0016	T
GERP RS		2.1
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9910163; hg19: chr17-26691321; COSMIC: COSV52647723; COSMIC: COSV52647723;